This invention relates to the field of the synthesis of amino aoids and, more particularly, to the synthesis of N-substituted amino acids by the reaction of glyoxal with a source of sulfur dioxide and either a primary amine, a secondary amine, or ammonia.
The N-substituted alpha-amino acids provided by the process of this invention have a number of important and varied uses. Some of these compounds can be employed as buffering agents in pharmaceutical and cosmetic preparations. Also, many can be employed as key intermediates in the manufacture of peptides, plastics, polymers, and herbicides. Exemplary of an intermediate employed in the production of a herbicide is the preparation of N-phosphonomethylglycine through N-benzylglycine as described in U.S. Pat. No. 3,835,000. The copending and coassigned application of Miller, et al., Ser. No. 687,404 filed Dec. 28, 1984, now abandoned, describes the preparation of N-phosphonomethyglycine salts by the dealkylation of N-alkyl-N-phosphonomethylglycine under alkaline conditions.
Because of its commercial importance, many processes for making glyphosate have been published. One conventional process for the manufacture of glyphosate is described by Hershman in U.S. Pat. No. 3,969,398. In that process, iminodiacetic acid is reacted with formaldehyde and phosphorous acid to produce an intermediate N-phosphonomethyliminodiacetic acid. This intermediate is oxidized to produce glyphosate.
Another process for the manufacture of glyphosate is described by Gaertner in U.S. Pat. No. 3,927,080. Gaertner describes the production of glyphosate wherein N-t-butyl-N-phosphonomethylglycine or its esters are hydrolyzed under acidic conditions. In the process of Gaertner, t-butylamine is reacted with a bromoacetate ester to produce an ester of N-t-butylglycine, which is in turn reacted with formaldehyde and phosphorous acid to produce the N-t-butyl-N-phosphonomethylglycine intermediate.
European Pat. No. 0,055,695 discloses a process for splitting off a substituent group from the nitrogen atom of an N-substituted N-phosphonomethylglycine by hydrogenolysis. The N-substituent is described as a 1-arylalkyl group suitable for hydrogenolytic cleavage. The hydrogenolytic process is carried out in the presence of a catalyst such as platinum or palladium on barium sulfate.
It may be noted that the various N-substituted amino acids play a prominent role in the processes which are available to the art for the manufacture of glyphosate. Thus, for example, the Hershman patent utilizes an iminodiacid directly in the synthesis of glyphosate, and the N-substituted glyphosates used in the synthesis schemes of Gaertner, European Pat. No. 0,055,695 can be prepared by phosphonomethylation of N-alkyl amino acids. Accordingly, there is a substantial need for economical methods for the preparation of N-substituted amino acids.
Moser U.S. Pat. Nos. 4,369,142 and 4,486,358 describes a method for the direct preparation of glyphosate by reacting aminomethylphosphonic acid with glyoxal, in an aqueous medium and in the presence of sulfur dioxide gas. ln the method described by Moser, a suspension of aminomethylphosphonic acid and glyoxal is initially prepared, after which sulfur dioxide is introduced into the suspension at 10.degree. to 15.degree. C. with vigorous stirring and cooling. Further cooling causes the glyphosate product to precipitate, after which it is recovered by filtration. In an alternative reaction scheme, a suspension of glyoxal-bis-(sodium hydrogen sulfite) and aminomethylphosphonic acid is refluxed with stirring. The glyphosate product is recovered by a series of acidification, evaporation, and crystallization steps.
Maurer and Woltersdorf, "Formation of amino acids from .alpha.-dicarbonyl compounds. Glycine derivatives from Glyoxal," Z. Physiol. Chem., 254, 18-24 (1938) describe the preparation of amino acid amides by heating glyoxal bisulfite in solution with aliphatic amines. Examples include the preparation of N,N-diethylglycinediethylamide, N-ethylglycineethylamide-HCl, and sarcosinemethylamide-HCl. The reference further reports production of the ethyl ester of N,N-diethylglycinate by heating diethylamine in ethyl alcohol with polymeric glyoxal, and distillation of the product.